Search

This study aimed to review the current state of the root caries field, explore the current hot topic, and anticipate future research frontiers. The Web of Science Core Collections was searched to acquire publications that were relevant to root caries from 1992 to 2021. After retrieval and manual screening, the co-occurrence and co-operation analysis of keywords and countries/institutions/authors were performed through CiteSpace and VOSviewer based on two periods (1992–2006 and 2007–2021). From 1992 to 2021, 451 unique publications were selected. The USA, which has been the center of international cooperation, has produced the most publications in the research area in 1992–2021. Journal of Dental Research and Caries Research are the main counterpart journals in the field of root caries. The University of London is the institution with the highest number of publications in the analyzed 30 years. “Demineralization,” “remineralization,” “aged,” “dentin,” and “fluoride” have been commonly used as keywords throughout the past 30 years. More studies from different aspects have been published in the field of root caries in recent years (2007–2021). The findings of this study provide a full picture of the last 30 years in this research area; hopefully, they also provide essential information for researchers and policymakers to make decisions.

Background: The CyberKnife© system combines real-time image guidance and a dynamic tracking system to implement frameless radiotherapy. This umbrella review is aimed to evaluate the effectiveness and safety of CyberKnife. Methods: A comprehensive search of health technology assessments and systematic reviews was performed among the Embase, PubMed and other grey databases until July 2020. Treatment outcomes were extracted, and the quality of included studies were assessed using AMSTAR-2. Results: Nineteen studies were eligible. CyberKnife not only had a wide range of applications, long overall survival and great local control, but also had a limited toxicity and good cost–effectiveness compared with other radiotherapy equipment. Conclusion: Despite the relatively low quality of the evidence, our findings can still provide a decision reference for policymakers.

Background: Hemostatic agents (HAs) are used to achieve hemostasis and prevent postoperative complications in multiple surgeries, but the role of HAs is ambiguous during partial nephrectomy (PN), so this study aimed to assess the role of HAs in PN. Methods: PubMed, Embase, CENTRAL and ClinicalTrials.gov were searched for randomized controlled trials and cohort studies regarding the comparison of HA use alone and standard suturing during PN on January 17, 2020. RevMan 5.3 was used to conduct meta-analysis. Sensitivity analyses and subgroup analyses were performed based on surgical procedures and HA types. Results: Six studies involving 1,066 patients were included. The quality of studies was moderate to high. There were significant reductions in warm ischemia time (mean difference [MD] = −6.30 min, 95% confidence interval [CI] −7.70 to −4.90, p < 0.00001), operative time (MD = −19.81 min, 95% CI −27.54 to −12.08, p < 0.00001), and estimated blood loss (MD = −108.62 mL, 95% CI −177.27 to −39.9, p = 0.002) in the HA group, and HA use alone did not increase postoperative complications. The results were similar in the subgroup analyses and sensitivity analyses. Conclusion: HA may be an effective and safe surgical material in PN, which can improve postoperative outcomes. High-quality and randomly designed studies are needed to validate the applicability.

Tongue squamous cell carcinoma is highly malignant with a poor prognosis. This study aimed to combine whole-genome sequencing, whole-genome methylation, and whole transcriptome analyses to better understand the molecular mechanisms of this cancer. Cancerous and paraneoplastic tissues from five patients with tongue squamous cell carcinoma were included as five paired samples. After multi-omics sequencing, differentially methylated intervals, methyl loop sites, methylated promoters, and transcripts were screened for variation in all paired samples. Correlations between them were analyzed to determine biological processes in tongue squamous cell carcinoma. We found five mutated methylation promoters that were significantly associated with the expression levels of mRNAs and lncRNAs. Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade, which is associated with cancer progression and the development of drug resistance during treatment. The prognostic signature models constructed based on the WDR81 and HNRNPH1 genes and combined clinical phenotype-gene prognostic signature models have shown high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings. We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs. Ultimately, changes in the transcript levels affect the prognosis of tongue squamous cell carcinoma patients.

To analyze the hot research topics and frontiers of preclinical dentistry education with bibliometric methods.We launched searches in the Web of Science Core Collection database to find relevant literature on preclinical dentistry education, with the time frame of the searches limited between the creation of the database and January 1, 2022. After data extraction, we used the CiteSpace software to conduct visualized analysis of a number of factors, including the number of publications, countries, institutions, authors, keywords, etc.A total of 322 articles and reviews were included in the study, and the annual publication volume showed a trend of steady growth in the past decade. With 98 papers, the United States had the most number of published papers. The United States and the United Kingdom were important countries in the national cooperation network. There were 10 institutions that published more than 5 articles. The total number of authors of the papers covered in the study was as many as 410. One author published 4 articles and was the most published author among them. The hot research topics of preclinical dentistry education included computer-assisted instruction, instructional methodology, clinical skills and 3D printing. Moreover, computer-assisted instruction was the new hot issue of the past decade. Besides, technology, restoration, clinic skills and communication skills were identified as novel research frontiers.Visualized analysis of the research literature generates an intuitive understanding of hot research topics and frontiers of preclinical dentistry education, which provides references for future studies.

Little research has been conducted to assess which specific databases should be searched when performing a systematic review (SR) on acupuncture. The current study aimed to identify key databases and the optimal database combination to retrieve randomized controlled trials (RCTs) on acupuncture for inclusion in SRs. A systematic search for SRs in the field of acupuncture was conducted in order to identify target databases and RCTs were extracted from the SRs that had searched all target databases. The proportions of SRs that had achieved 100%, 95%, or 90% recall of RCTs and the total recall of RCTs in various combinations of target databases were calculated. Sensitivity analysis was performed on those SRs that included 10 or more RCTs. CNKI, WanFang, VIP, PubMed, CENTRAL and Embase were regarded as target databases. A total of 4349 acupuncture RCTs were extracted from 286 SRs. Searching all six target databases retrieved 99.3% of all RCTs while 99.1% were recalled by searching the combination of CNKI, WanFang, PubMed and CENTRAL. There were no significant differences on total recall of RCTs (p = 0.549) or in the proportion of SRs with 90% recall of RCTs (97.2% vs. 97.6%; p = 0.794) between searching the above four and the full six target databases. Most results were similar in the sensitivity analysis. The combined retrieval power of CNKI, WanFang, PubMed and CENTRAL was considered an efficient choice to retrieve acupuncture RCTs included in SRs.

The oral microbiome contains numerous bacteria, which directly or indirectly participate in various human functions and continuously exchange signals and substances with the human body, significantly affecting human life cycle, health, and disease. This study aimed to conduct bibliometric studies on the scientific outputs of global oral microbiome research by Citespace software. The data were obtained from the Thomson Reuters' Web of Science Core Collection (WoSCC), from the first relevant literature published until December 31st, 2019, and a total of 2225 articles and reviews were identified. The top country and institutions are the United States and Harvard University. Keywords analysis showed that periodontal disease, oral microbes, and dental plaque are research hotspots. The burst word analysis indicates that early childhood caries, squamous cell carcinoma, gut microbiome, Helicobacter pylori, Candida albicans, and dysbiosis are likely to become the research hotspots of the next era. We also recommend the use of knowledge mapping methods to track specific knowledge areas efficiently and objectively regularly, which can accurately identify hotspots and frontiers and provide valuable information for practitioners in the field, including related scientists, students, journals, and editors., This study aimed to study the scientific outputs of the global oral microbiome research. The data were obtained from the WoSCC, from the earliest literature to December 31st, 2019. Interesting insights are discovered, such as research hotspots and frontiers. We recommend using bibliometric methodology to dynamically monitor a specific field to achieve comprehensive understanding and trend on a regular basis.

Macroautophagy (hereafter referred to as autophagy) is a highly conserved catabolic eukaryotic pathway that is critical for stress responses and homeostasis. Atg18, one of the core proteins involved in autophagy, belongs to the PROPPIN family and is composed of seven WD40 repeats. Together with Atg2, Atg18 participates in the elongation of phagophores and the recycling of Atg9 in yeast. Despite extensive studies on the PROPPIN family, the structure of Atg18 from Saccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 Å. Based on bioinformatics and structural analysis, we found that the 7AB loop of ScAtg18 is extended in Atg18, in comparison to other members of the PROPPIN family. Genetic analysis revealed that the 7AB loop of ScAtg18 is required for autophagy. Biochemical and biophysical experiments indicated that the 7AB loop of ScAtg18 is critical for interaction with ScAtg2 and the recruitment of ScAtg2 to the autophagy-initiating site. Collectively, our results show that the 7AB loop of ScAtg18 is a new binding site for Atg2 and is of functional importance to autophagy.

Super elongation complex (SEC) is a positive regulator of RNA polymerase II, which is required for HIV-1 proviral transcription. AFF1/4 is the scaffold protein that recruits other components of SEC and forms dimer depending on its THD domain (TPRL with Handle Region Dimerization Domain). Here we report the crystal structure of the human AFF4-THD at the resolution of 2.4 Å. The α4, α5, and α6 of one AFF4-THD mediate the formation of a dimer and pack tightly against the equivalent part of the second molecule in the dimer of AFF-THD. Mutagenesis analysis revealed that single mutations of either Phe1014 or Tyr1096 of AFF4 to alanine impair the formation of the AFF4 dimer. In addition, transactivation assay also indicated that Phe1014 and Tyr1096 of AFF4 are critical to the transactivation activity of AFF4. Interestingly, the corresponding residues Phe1063 and Tyr1145 in AFF1 have an effect on the transactivation of HIV-1 provirus. However, such mutations of AFF1/4 have no effect on the interaction of AFF1/4 with other subunits of the SEC. Together, our data demonstrated that the dimerization of AFF1/4 is essential to transactivation of HIV-1 provirus.

Numerous studies suggested methylation modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted DNA methylation architecture on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references when managing UTUC patients.PubMed, Cochrane Library, EMBASE, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Meta-analysis was conducted to assess the prognostic effect of methylated genes. Kaplan-Meier survival analyses were performed to validate methylated genes and cytosine-phosphate-guanine (CpG) sites.Eleven studies (3619 patients) were eligible to investigate 12 methylated genes and 10 CpGs. The quality of all the studies was fair to good. Meta-analysis found the pooled effect of eligible methylated genes had a low risk of tumor recurrence (HR = 0·67; 95% CI: 0·51-0·87; P = ·003), but a high risk of tumor progression (HR = 1·60; 95% CI: 1·17-2·18; P = ·003) and cancer-specific mortality (HR = 1·35; 95% CI: 1·06-1·72; P = ·01). For individual methylation status of GDF15, HSPA2, RASSF1A, TMEFF2, and VIM, the pooled effect of each gene was found pleiotropic on both diagnosis and prognosis. Survival analysis suggested higher methylation of SPARCL1 had a better disease-specific survival (P = ·048).We combined meta-analysis and Kaplan-Meier survival analysis using the most updated evidence on the methylation of UTUC. Candidate biomarkers with essential diagnosis and prognosis function might provide precision medicine references for personalized therapies.

Numerous studies suggested that non-coding RNA modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted the architecture of non-coding RNA on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references of non-coding RNA when managing UTUC patients. PubMed, Cochrane Library, Embase, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Enrichment analyses and network analyses were conducted to explore the interactions of miRNA with genes and other non-coding RNAs. Survival analyses were performed to validate the novel genes. A total of 12 pairs of UTUC tumors and adjacent normal tissues were also included to validate the gene expressions regulated by miRNAs from the miRNA-gene network. Thirteen studies with 945 patients were eligible, investigating 106 miRNAs mutations. The quality of all the studies was fair to good. Most miRNAs were enriched in tissue/organs, diseases, and specific anti-cancer drugs (false discovery rate0.05). Other non-coding RNAs, i.e.,: miR-34a, DLGAP1-AS1, USP39, and RNA5SP479, were highlighted by network analyses to have potential in the pathogenesis of UTUC. Top hub genes in the miRNA-gene network, namely ZNF460, NUFIP2, and E2F3, were all validated by survival analysis(P0.05). Using own cohort data, the differential expression analyses identified 368 overlapped significant genes, including above 3 hub genes (false discovery rate0.05). Novel biomarkers identified in our studies might play essential roles in UTUC, from the perspectives of the molecule, tissue/organ, diagnosis, treatment, and prognosis. Candidate biomarkers could be significant references for personalized and target therapies.

An umbrella review on the effectiveness and safety of the CyberKnife

Eating monitoring has remained an open challenge in medical research for years due to the lack of non-invasive sensors for continuous monitoring and the reliable methods for automatic behavior detection. In this paper, we present a pilot study using the wearable 24-hour ECG for sensing and tailoring the sophisticated deep learning for ad-hoc and interpretable detection. This is accomplished using a collocative learning framework in which 1) we construct collocative tensors as pseudo-images from 1D ECG signals to improve the feasibility of 2D image-based deep models; 2) we formulate the cardiac logic of analyzing the ECG data in a comparative way as periodic attention regulators so as to guide the deep inference to collect evidence in a human comprehensible manner; and 3) we improve the interpretability of the framework by enabling the backtracking of evidence with a set of methods designed for Class Activation Mapping (CAM) decoding and decision tree/forest generation. The effectiveness of the proposed framework has been validated on the largest ECG dataset of eating behavior with superior performance over conventional models, and its capacity of cardiac evidence mining has also been verified through the consistency of the evidence it backtracked and that of the previous medical studies.

Objective: To identify a comprehensive list of outcomes and explore the reporting rate of core outcome sets (COS) and related factors in systematic reviews (SRs) of acupuncture for osteoarthritis (OA). Study design and setting: Databases were searched for the relative SRs. Descriptive statistics were calculated as frequencies and percentages. Binary logistic regression was used to explore the factors affecting the reporting rate of COS. Results: We included 59 SRs. Outcome measures reported in the SRs were classified into 11 domains and 67 unique outcomes. No SR completely reported COS. In COS released in 2016, 75% of outcomes (6/8) were only reported by ⩽5% SRs. In COS released in 2019, the reporting rate was very low (from 0% to 17%) for 73.3% of outcomes (11/15). SRs published in the most recent 5 years had a significantly greater possibility of reporting COS (odds ratio (OR) = 4.74, 95% confidence interval (CI) = 1.33 to 16.88, p = 0.016). Conclusion: Core outcomes were rarely reported in systematic reviews of acupuncture for OA, with considerable heterogeneity in the use of outcomes. The publication of COS in the COMET (Core Outcome Measures in Effectiveness Trials) database may help promote the reporting of COS. We encourage systematic reviewers to use relevant COS.

Background 5-Fluorouracil (5-FU) is an essential chemotherapeutic agent for oral squamous cell carcinoma (OSCC). However, toxic side effects have limited its role in OSCC therapy. The aim of this study was to explore whether combination therapy with 5-FU and honokiol (HNK), a small natural organic molecule shown to induce apoptosis in OSCC cells, could enhance the anticancer activity of 5-FU without notably increasing its toxicity. Methods 5-FU and/or HNK were used to treat OSCC cells both in vitro and in vivo. The therapeutic effect and underlying mechanisms were evaluated by cell viability assay, flow cytometry, OSCC xenograft mouse model, and Western blot. Tumor tissue apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Toxicity was assessed following hematoxylin and eosin staining. Results Exposure to HNK + 5-FU produced a synergistic cytotoxic effect on OSCC cells. Both HNK and 5-FU could induce apoptosis through the mitochondria-mediated intrinsic pathway, and their specific signaling pathways were different. In the mouse OSCC xenograft model, treatment with 5-FU + HNK substantively retarded tumor growth, as compared to treatment with either drug individually. TUNEL analysis further confirmed that the superior in vivo antitumor efficacy of 5-FU + HNK was associated with enhanced stimulation of cell apoptosis. Notably, HNK did not increase the toxicity of 5-FU. Conclusion These findings suggest that HNK and 5-FU exert a synergistic therapeutic effect on OSCC by inducing apoptosis. HNK might thus enhance the clinical therapeutic efficacy of 5-FU without increasing its toxicity.

Summary Background PA28γ was suggested to play a role in malignant progression. This paper aimed to investigate the association between PA28γ and the prognosis of oral squamous cell carcinoma (OSCC) in cohort studies. Methods The PA28γ expression level was assessed by immunohistochemistry in a total of 368 OSCC patients from three independent cohorts. The Cox proportional hazards regression model was used to determine multivariate hazard ratios for Overall Survival (OS). Model discrimination was measured using C Statistic. Additionally, OS was analyzed in Head Neck Squamous Cell Carcinoma (HNSCC) patients from The Cancer Genome Atlas (TCGA) data set. Functional analyses were conducted both in-vitro and in-vivo. Findings The median follow-up times of patients in the three studies were 60, 52, and 51 months. High expression of PA28γ was identified in tumors from 179 of 368 patients (48.6%). Compared with low expression, high expression of PA28γ was strongly associated with worse OS, with relative risks of 5.14 (95% CI, 2.51–10.5; P, Highlights • PA28γ protein over-expressed in a large subset of patients with OSCC • PA28γ was a prognostic factor in OSCC based on the results of three cohorts in China • The analysis of PA28γ mRNA abundance in a US/non-Chinese cohort from TCGA dataset consistent with Chinese-cohort study • PA28γ silencing could affect the tumor biological behavior of OSCC both in vitro and vivo.

Integrins, which act as an important role in the connection between cells and extra-cellular environments, are important cell surface receptors. Integrins have been demonstrated to play critical roles in many aspects of the progression of oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in microRNA-binding sites of integrin genes and the susceptibility and progression of OSCC in Chinese Han Population. We recruited 167 OSCC patients and 200 cancer-free controls from three independent medical centers. Genotyping was completed successfully for the five selected integrin SNPs: rs1062484 (integrin α3), rs11902171 (integrin αv), rs17468 (integrin β1), rs3809865 (integrin β3), and rs2675 (integrin β5). The results demonstrated that the A allele of rs3809865 T/A (a T-to-A nucleotide change), a functional polymorphism in the 3'UTR of integrin β3 gene, was associated with OSCC risk (p < 0.05). In addition, the association analysis between this SNP and integrin β3 mRNA expression level in the patients' peripheral blood mononuclear cells indicated that OSCC patients carrying the A allele would have a lower integrin β3 expression level (p = 0.047). Meanwhile, survival analysis showed that the C allele of rs2675 A/C (nucleotide change from A to C), another 3'UTR polymorphism in integrin β5 gene, was related with progression of OSCC. Overall, our results suggest that rs3809865 and rs2675 may contribute to OSCC risk and progression in Chinese Han Population. These two SNPs may be used as potential diagnostic and prognostic biomarkers for OSCC in future.

Our previous salivary study had demonstrated an apparent T helper 2 (Th2)-predominance in saliva of oral lichen planus (OLP) patients and suggested a potential of salivary interleukin-4 (IL-4) as a biomarker for monitoring disease severity. To further determine the consistency of Th1/Th2 bias of OLP, this study investigated the expression profile of interferon-γ (IFN-γ) and IL-4 in serum and the relationship of the serum levels of these cytokines with their saliva partners. Sixty ethnic Chinese patients with OLP (40 of the erythematous/ulcerative form and 20 of the reticular form) were recruited for this study, with 40 age-sex-matched healthy volunteers as control group. IFN-γ and IL-4 levels in serum and paired saliva samples were screened by enzyme-linked immunosorbent assay. OLP patient showed a low-level IFN-γ but high-level IL-4 expression profile in both serum and saliva, with a lower IFN-γ/IL-4 ratio. Serum IL-4 level in the erythematous/ulcerative group was significantly higher than that in the reticular group. Serum levels of IFN-γ and IL-4 were significantly and positively correlated with their saliva partners. These results provided more evidence for Th2 cytokine-predominant immune imbalance in OLP, as well as the potential of IL-4 as the biomarker for monitoring severity of OLP.

In vivo engineering of bone autografts using bioceramic scaffolds with appropriate porous structures is a potential approach to prepare autologous bone grafts for the repair of critical-sized bone defects. This study investigated the evolutionary process of osteogenesis, angiogenesis, and compressive strength of bioceramic scaffolds implanted in two non-osseous sites of dogs: the abdominal cavity and the dorsal muscle. Hydroxyapatite (HA) sphere-accumulated scaffolds with controlled porous structures were prepared and placed in the two sites for up to 6 months. Analyses of retrieved scaffolds found that osteogenesis and angiogenesis were faster in scaffolds implanted in dorsal muscles compared with those placed in abdominal cavities. The abdominal cavity, however, can accommodate larger bone grafts with designed shape. Analyses of scaffolds implanted in abdominal cavities [an environment of a low mesenchymal stem cell (MSC) density] further demonstrated that angiogenesis play critical roles during osteogenesis in the scaffolds, presumably by supplying progenitor cells and/or MSCs as seed cells. This study also examined the relationship between the volume of bone grafts and the physiological environment of in vivo bioreactor. These results provide basic information for the selection of appropriate implanting sites and culture time required to engineer autologous bone grafts for the clinical bone defect repair. Based on these positive results, a pilot study has applied the grafts constructed in canine abdominal cavity to repair segmental bone defect in load-bearing sites (limbs).

Tumor necrosis factor-alpha (TNF-α) has been proposed to contribute to the development of upper aerodigestive tract (UADT) cancer that is characterized by poor prognosis. The G-to-A nucleotide change at -308 of the TNF-α gene (-308G/A polymorphism) can increase the expression level of TNF-α and thus may affect the genetic susceptibility of UADT cancer. The association between the -308G/A polymorphism and UADT cancer has been widely studied, but the results published are quite controversial. To obtain a more precise conclusion, we performed a meta-analysis including 1,751 patients and 3,345 controls. The results indicated that the AA genotype of the -308G/A polymorphism had a 54%-increased risk of UADT cancer, compared with the G carriers (GG and GA genotypes) [odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.07-2.21]. After stratified by ethnicity, the AA genotype was associated with increased risk of UADT cancers in South Asians (OR = 33.18 and 95% CI: 1.92-573.62 for AA vs. GA+GG) but not in Caucasians or East Asians. After stratified by tumor site, the -308G/A polymorphism was associated with increased risks of oropharynx cancer (OR = 2.68 and 95% CI: 1.34-5.35 for AA vs. GA+GG) but not associated with esophagus or larynx cancer. After stratified by histological type, the -308G/A polymorphism was associated with increased risks of squamous cell carcinoma (OR = 1.81 and 95% CI: 1.15-2.84 for AA vs. GA+GG) but not associated with adenocarcinoma. Our results indicate that the -308G/A polymorphism might contribute to an increased risk of UADT cancer susceptibility.

Background Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC. Methods The expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown. Results PA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors. Conclusions These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0309-z) contains supplementary material, which is available to authorized users.

microRNAs (miRNA) silence target genes through Watson-Crick based binding to the 3'untranslated regions (3'UTR). Thus, polymorphisms in the miRNA-binding sites may disrupt this process and play a potential role in cancer pathogenesis. Integrins have been implicated in the genesis and development of many tumors. This study was designed to evaluate the association between five SNP loci in predicted miRNA-binding sites in five integrin genes and prostate cancer occurrence and prognosis to provide data for screening high-risk Chinese Han individuals. These five polymorphisms were genotyped by using the high-resolution melting method (HRM) in 347 Chinese Han prostate cancer patients with long-time follow-up together with 367 age-matched healthy controls. GC carriers of rs11902171 in ITGAv were associated with a decreased risk of prostate cancer (OR 0.57, 95% CI 0.35-0.93). However, no significant difference was detected in genotype distributions of the five SNP loci in the progression-free survival time of prostate cancer. The ITGAv gene SNP rs11902171 may be potentially associated with the risk of prostate cancer.

Single-nucleotide polymorphisms located in the microRNA biogenesis pathway could alter the risk for developing prostate cancer. The present study was intended to identify common genetic variants responsible for prostate cancer susceptibility in the GEMIN4 gene. The high-resolution melting method was used to genotype seven polymorphisms (rs7813, rs4968104, rs3744741, rs2740348, rs1062923, rs910925, and rs910924) in the GEMIN4 gene in 300 prostate cancer patients and 244 matched controls. The encouraging discovery in this study was in the rs2740348. Patients carrying the variant heterozygote GC genotype in the rs2740348 were at a 36% decreased risk of prostate cancer (odds ratio [OR] = 0.64; 95% confidence interval [CI] = 0.42, 0.99). Similarly, this variant allele carrier showed significant risk for prostate cancer (OR = 0.64). In addition, subjects carrying the homozygote TT genotype in the rs7813 had a significantly increased risk of prostate cancer (OR = 2.53, 95% CI = 1.07, 6.28). Two common haplotypes were found to be associated with decreased risk of prostate cancer. In the subgroup analysis, higher risk of more severity of prostate cancer (clinical stage III and IV) was observed in individuals with the rs7813 TT genotype (OR = 2.64, 95% CI = 1.02, 7.64), while lower risk of more severity of prostate cancer was observed in individuals with the rs3744741 T allele (OR = 0.69, 95% CI = 0.50, 0.96). Overall, our study provides substantial support for the association between the GEMIN4 gene and the risk of prostate cancer.

Receptor of activated protein kinase C 1 (RACK1) has been identified as an anchoring or adaptor protein in multiple intracellular signal transduction pathways. Our previous study has showed that the expression of RACK1 was paralleled with proliferation and correlated with metastasis and clinical outcome. However, the underlined mechanism has not been uncovered. We first selected a most effective siRNA among three siRNAs (siRNA-1, siRNA-2 and siRNA-3) targeting different regions in the RACK1 mRNA and re-evaluated the anticancer effect of RACK1 silencing on HSC-3 and Cal-27 cell lines by cell growth inhibition. And then, we investigated whether knockdown of RACK1 could inhibit cell adhesion, migration and invasion in these two cell lines. To further understand the molecular mechanism of RACK1 in these processes, the expressions of EGFR, pEGFR, HER2, MMP-2 and MMP-9 were detected by western blot. We verified that the silence of RACK1 gene in two OSCC cell lines could not only inhibit cell proliferation but also decrease the invasion, migration and adhesion capability of the tumor cells. Further, western blot analysis deduced that it might be related to the decrease in protein expression of EGFR, pEGFR, HER2, MMP-2 and MMP-9. Our results clearly showed the significance of RACK1-induced OSCC cell migration, invasion and adhesion, which could explain the underlined mechanism of the effect of the gene on metastasis and clinical outcome. Also, our results confirmed its role to be a prognostic indicator and a promising drug target for OSCC cell metastasis.

Many reports have shown that the biologic rhythm could be altered due to mutations of circadian gene hClock or hPeriod, and the mutations of circadian genes have some relationship with psychosis according to recent studies. A preliminary study has been conducted to examine wether the T3111C single nucleotide polymorphism of the hClock gene or the length polymorphism of the hPer3 gene is associated with the development of schizophrenia. The samples from schizophrenics (n=148, male: 57.4%, female: 42.6%) and normal controls (n=199, male: 59.3%, female: 40.7%) were examined. Allele frequencies of T3111C SNP of hClock were significantly different between schizophrenics and controls (χ2=19.738, P0.05). Schizophrenics had a significantly higher frequency of the C allele compared with controls (OR=2.613, 95% CI=1.693-4.034). On the other hand, there is no significant difference of allele frequencies of 18 exon of hper3 between schizophrenics and controls (χ2=0.192, P0.05). Our results suggest that the T3111C (RS1801260) polymorphism of hClock gene is associated with schizophrenia, but it seems that the length polymorphism of 18 exon of hPer3 may not be associated with schizophrenia. It is important to address of the relationship between circadian gene polymorphisms and dopamine functions in further study.

INTRODUCTION:Knotless barbed sutures can eliminate knot tying during the bariatric surgery (BS) (1). Since effects reported by patients and surgeons are ambiguous, the aim of this study was to establish the safety and efficacy of barbed sutures for intestinal sutures to close the gastrojejunal anastomosis in obese patients undergoing BS.METHODS:PubMed, EMBASE, Cochrane Register of Clinical Studies, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) and cohort studies comparing barbed sutures with conventional sutures in BS (until 30 June 2016). Quality assessment was conducted using to Cochrane recommendations. Review Manager was applied to analyze the data, and we sequentially omitted each study to perform sensitivity analyses.RESULTS:A total of five cohort studies (low to moderate risk of bias) (n = 859), and no RCTs provided eligible patients. BS includes laparoscopic Roux-en-Y gastric bypass and Laparoscopic sleeve gastrectomy. Comparing to conventional sutures, pooling data showed that suture time (Mean Difference, MD = -5.73, 95 percent Confidence Interval, CI -6.25 to -5.21, P < .01) and operative time (MD = - 7.67, 95 percent CI -10.49 to -4.85, P < .01) decreased significantly in the barbed group. Although the postoperative complications did not suggest significant changes (Odds Ratio, OR = 1.56, 95 percent CI .79 to 3.07, P = .2), the pooling results of hospital stay suggested that a significantly longer duration happened in the barbed groups, despite the fact that there may be only 0.18 day longer. (MD =0.18, 95 percent CI .06 to .29, P = .003).CONCLUSIONS:The barbed suture is an effective and safe surgical technique in BS. More evidence with randomized design, larger sample sizes and longer follow up need to compel validations of this state-of-the-art product in the future (2,3).

INTRODUCTION:Knotless barbed sutures can eliminate knot tying when patients are undergoing cosmetic surgery (CS). Although benefits reported on clinical outcomes are obvious, many studies have failed to demonstrate the potential for barbed sutures to mitigate adverse events. Thus, this study aimed to determine the safety of knotless barbed suture in CS.METHODS:PubMed, EMBASE, Cochrane Register of Clinical Studies, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) and cohort studies comparing barbed sutures with conventional sutures in CS (until 30 June 2016). Quality assessment was conducted using Cochrane recommendations. Review Manager was applied to analyze the data, and we sequentially omitted each study to perform sensitivity analyses.RESULTS:A total of five RCTs (low to moderate risk of bias) and six cohort studies (low to moderate risk of bias), proved eligible (3,481 patients). The CS included body contouring operations, breast reconstruction, lipoabdominoplasty, abdominoplasty and wound closure of cesarean delivery. Comparing to conventional sutures, pooling data showed that general adverse events of barbed sutures were not significantly different (Odds Ratio, OR = .6, 95 percent Confidence Interval, CI .24 to 1.52, P = .28), while the subgroup analysis showed that fewer adverse events occurred in cohort studies, though with high heterogeneity (I2 = 87 percent). Specifically, no significant differences were shown between barbed and traditional sutures in wound dehiscence (OR = .55, 95 percent CI .29 to 1.03, P = .06), incisional infection (OR = .56, 95 percent CI .22 to 1.48, P = .25), seroma (OR = .87, 95 percent CI .42 to 1.79, P = .70) and hematoma (OR = 1.52, 95 percent CI .29 to 7.99, P = .62).CONCLUSIONS:No differences were found between knotless barbed sutures and conventional sutures generally, but the cohort studies suggested barbed sutures resulted in fewer adverse events with longer follow-up. Thus barbed sutures are considered a safe surgical technique in CS. More evidence with larger sample sizes and longer follow up are needed to confirm the advantages of this technique in the future.

Background AKT1 is an important downstream effector of PTEN/PI3K/AKT signal transduction pathway. Aberrant expression and genetic variant of AKT1 gene are suggested to be involved in several types of human cancers, including OSCC. The aim of this study was to investigate the possible association between AKT1 gene polymorphisms and OSCC in Chinese Han Population. Methods A total of 182 OSCC patients and 207 cancer-free controls were enrolled for this hospital-based study. Five single-nucleotide polymorphisms (SNPs) on AKT1 (rs1130214, rs1130233, rs2494732, rs3730358, rs3803300) were investigated and genotyped by Sequenom Mass ARRAY & iPLEX-MALDI-TOF technology. Chi-square test, SHEsis software, and Kaplan–Meier method were used to evaluate the relationship between selected SNPs and OSCC susceptibility and progression. Results Significant difference of genotype distribution was observed between cases and control group at SNP sites rs1130214 (P = 0.006) and rs3803300 (P = 0.033, P = 0.003 for heterozygote and homozygous mutant, respectively). In the haplotype analysis, haplotype H4 which contained mutant-type allele of rs1130214 and rs3803300 was also related to OSCC risk (OR = 1.974, 95% CI = 1.048–3.718). Moreover, CT genotype of rs3730358 was associated with higher risk of OSCC progression (HR = 2.466, 95% CI = 1.017–5.981). Conclusion Our results indicated that rs1130214 and rs3803300 were related to OSCC susceptibility in Chinese Han Population. In addition, rs3730358 might be associated with progression-free survival time of OSCC patients, suggesting that this SNP could be a potential prognosis marker for OSCC.

BACKGROUND: Human beta-defensin-1 (hBD-1) has recently been considered as a candidate tumor suppressor in renal and prostate cancer. The aim of this study was to investigate the role of hBD-1 in the progression of oral squamous cell carcinoma (OSCC) and its potential as diagnostic/prognostic biomarker and therapeutic target for OSCC. METHODS: HBD-1 expression in tissues at different stages of oral carcinogenesis, as well as OSCC cell lines was examined. HBD-1 was overexpressed in HSC-3, UM1, SCC-9 and SCC-25 cells and subjected to cell growth, apoptosis, migration and invasion assays. Tissue microarray constructed with tissues from 175 patients was used to examine clinicopathological significance of hBD-1 expression in OSCC. RESULTS: HBD-1 expression decreased from oral precancerous lesions to OSCC and was lower in OSCC with lymph node metastasis than those without metastasis. In vitro, the expression of hBD-1 was related to the invasive potential of OSCC cell lines. Induction of exogenous expression of hBD-1 inhibited migration and invasion of OSCC cells, probably by regulation of RhoA, RhoC and MMP-2; but had no significant effect on proliferation or apoptosis. In a cohort of patients with primary OSCC, cases with no expression of hBD-1 had more chance to be involved in lymph node metastasis. Eventually, the positive expression of hBD-1 was associated with longer survival of patients with OSCC, and multivariate analysis and ROC curve analysis confirmed hBD-1 positivity to be an independent prognostic factor of OSCC, especially OSCC at early stage. CONCLUSIONS: Overall, these data indicated that hBD-1 suppressed tumor migration and invasion of OSCC and was likely to be a prognostic biomarker and a potential target for treatment of OSCC.

In vivo engineering of bone autografts using bioceramic scaffolds with appropriate porous structures is a potential approach to prepare autologous bone grafts for the repair of critical-sized bone defects. This study investigated the evolutionary process of osteogenesis, angiogenesis, and compressive strength of bioceramic scaffolds implanted in two non-osseous sites of dogs: the abdominal cavity and the dorsal muscle. Hydroxyapatite (HA) sphere-accumulated scaffolds with controlled porous structures were prepared and placed in the two sites for up to 6 months. Analyses of retrieved scaffolds found that osteogenesis and angiogenesis were faster in scaffolds implanted in dorsal muscles compared with those placed in abdominal cavities. The abdominal cavity, however, can accommodate larger bone grafts with designed shape. Analyses of scaffolds implanted in abdominal cavities [an environment of a low mesenchymal stem cell (MSC) density] further demonstrated that angiogenesis play critical roles during osteogenesis in the scaffolds, presumably by supplying progenitor cells and/or MSCs as seed cells. This study also examined the relationship between the volume of bone grafts and the physiological environment of in vivo bioreactor. These results provide basic information for the selection of appropriate implanting sites and culture time required to engineer autologous bone grafts for the clinical bone defect repair. Based on these positive results, a pilot study has applied the grafts constructed in canine abdominal cavity to repair segmental bone defect in load-bearing sites (limbs).

Background A large number of meta-analyses and pooled analyses have been published on the topic of the genetic variants for oral cancer, and many positive results have been identified; however, there might be some false-positive results. The aim of this study was to identify the ‘true positive’ (noteworthy) results using the method of false-positive report probability (FPRP). Methods The PubMed database, Embase database, CNKI database, and Wanfang database were searched to retrieve the meta-analyses, pooled analyses, and genome-wide association studies (GWAS), which addressed the associations between genetic polymorphisms and the risk of oral cancer. The significant associations were further analyzed using the method of FPRP. Results A total of 14 variants were identified from meta-analyses and pooled analyses, which concern the associations between oral cancer and genetic variants. Among these 14 variants, 9 variants were reported to be significantly associated with the risk of oral cancer (CYP1A1-MspI, CYP2E1-RsaI/PstI, MTHFR-C677T, p73-G4C14-to-A4T14, XRCC1-Arg194Trp, CYP1A1-Ile462Val, GSTM1-±, and NAT2 slow vs rapid). After assessing the results of FPRP, none of the nine statistically significant associations were noteworthy (true positive). In addition, no noteworthy results were identified from GWAS. Conclusions In summary, this study found no noteworthy associations between variants and the risk of oral cancer. Further candidate genes associations studies should be performed to explore the etiology of oral cancer.

Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancer development. However, results from the published reports have remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene and cancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for case- control studies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Three IL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies were analyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk when all studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allele carriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI = 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associated with a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison: OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with a decreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison: OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians (heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with a decreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups. Future case-control studies with large sample size are needed to evaluate these associations in detail.

We aimed to investigate the association between the expression of phosphorylated Akt(Thr308) (p-Akt(Thr308)) in oral squamous cell carcinoma (OSCC) tissues and clinicopathological parameters of OSCC patients and to verify the validity of p-Akt(Thr308) as a prognostic biomarker.One hundred and ninety-one patients with OSCC were recruited for the study. We tested the expression of p-Akt(Thr308) by immunohistochemistry (IHC) with tissue microarray (TMA) and analyzed with digital pathology analysis software. The clinicopathological parameters of all patients were collected from follow-up.P-Akt(Thr308) was detected in 95.2% of OSCC patients. The expression of p-Akt(Thr308) was significantly correlated with local recurrence and five-year survival rate. High expression of p-Akt(Thr308) in OSCC was associated with poor prognosis.P-Akt(Thr308) might be a candidate biomarker for the prediction of OSCC prognosis.